Abstrato

The role of vascular endothelial growth factor and mesenchymal stem cells during angiogenesis

Nanae Oki, Takaharu Abe, Ryo Kunimatsu, Keisuke Sumi, Tetsuya Awada, Yuji Tsuka, Kengo Nakajima, Kazuyo Ando, Kotaro Tanimoto

Objective: Angiogenesis is essential for bone remodeling and regeneration. We previously showed that 3 months after transplantation of mesenchymal stem cells (MSCs) into a bone defect area, significantly more regenerated bone was present on the MSC side than on the control side. On the side transplanted with MSCs, the number of blood vessels was significantly higher. Therefore, during the remodeling process, MSCs, which are necessary for regenerating bone, were involved in bone regeneration through angiogenesis in the transplanted area. In addition, MSCs produce Vascular Endothelial Growth Factor (VEGF). Therefore, we investigated the influence of differentiation of MSCs on the expression of VEGF.

Methods: We investigated how changes in osteogenic differentiation of MSCs affect VEGF gene and protein expression and how co-culture with Human Umbilical Vein Endothelial Cells (HUVECs) affects gene expression in MSCs. We also determined the role MSCs play in the transplanted area, and the effects on HUVEC morphology when co-cultured with MSCs.

Results: VEGF gene and protein expression in undifferentiated MSCs was higher than in differentiated MSCs. VEGF gene expression in MSCs co-cultured with HUVECs was higher than when MSCs were cultured alone. In co-cultures of MSCs and HUVECs, a lumen-like structure was observed on the 3rd day of culture, and then several luminal structures were observed later.

Conclusion: MSC transplantation may contribute to angiogenesis via production of VEGF.